The chromaffin cells of canine adrenal medulla served as a model to study the regulation of the cholinergic nicotinic receptor. The role of GABAA receptors in the regulation of the release of catecholamine and met-enkephaline-like (ME) peptides was studied in situ by autoperfusion of the adrenal gland. Infusion into the adrenal gland of GABAA receptor antagonists increased the release of catecholamines and ME-peptides into the adrenal effluent blood. This release was attenuated by GABAA receptor antagonists, but not by hexamethonium, naloxone or prior splanchnic nerve transection. In contrast, the extent of release of catecholamines and ME-peptides elicited by splanchnic nerve stimulation was decreased by GABAA receptor agonists and facilitated by GABAA receptor antagonists. These data suggest that the release of these neurotransmitters may be triggered by direct stimulation of GABAA receptors, presumably causing membrane depolarization by a burst of chloride channel opening. This type of depolarization may be responsible for obtunding the subsequent depolarizing effect of nicotinic receptor stimulation.